pH is an extremely important parameter of metabolic regulation at virtually every level of biological organization. Changes in pH are associated with a variety of metabolic and pathological states. The purpose of the proposed investigation is to develop semi-permeant weak acids and bases which will allow sensitive and rapid determination of intracellular and whole-body pH using 19F Nuclear Magnetic Resonance (NMR) spectroscopy. The Fluorine labeled weak acids and bases will be designed to be ideally-behaving, non-toxic and semi-permeable compounds, with pKa's in the range of 6.0-8.0. Adequate knowledge is available to design compounds that fit these criteria. Several preliminary designs are included which should satisfy these requirements. The compounds will also be hexafluorinated which will give a substantial increase in sensitivity over monofluorinated compounds. The ramifications of such a technique will be enormous. At the cellular level, using high-field NMR, this technique will allow simultaneous and rapid determination of the pH inside various compartments, such as cytosol, nucleus, mitochondria and vesicles. This technique could also be combined with other 19F NMR methods to allow simultaneous determination of pH, Ca++ and Na+ in whole cells. At the organismal level using Topical Magnetic Resonance (TMR), this technique will allow rapid, compartymentalized, pH determinations to be performed on selected organ systems in vivo. It is also planned that this technique will be applicable to whole-body pH determinations using the technique of NMR imaging.